We report 2 cases of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer successfully treated with a combination therapy of S-1, cisplatin( CDDP), and trastuzumab followed by curative resection. Case 1 involved a 62-year-old man with type 3 HER2-positive gastric cancer spanning the antrum of the stomach to the duodenal bulb and directly invading the pancreatic head( cT4b[ Panc] N3H0P0M0, Stage IIIC). We diagnosed it as an unresectable cancer, and selected S-1, CDDP, and trastuzumab for combination chemotherapy. S-1 (120 mg/body/day) was administered orally for 2 weeks, followed by 1 drug-free week as a course, and CDDP (60 mg/m2) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance) were administered by intravenous infusion on day 1. After the third course, significant tumor and lymph node reduction was observed; however, pyloric stenosis developed. Distal gastrectomy with D2 lymphadenectomy was performed. Case 2 involved a 62-year-old woman with type 4 HER2-positive gastric cancer from the angle of the stomach to the duodenal bulb and directly invading the pancreatic head (cT4b [Panc] N2H0P0M0, Stage IIIC). After the third course of combination therapy, significant tumor reduction and disappearance of lymph nodes metastasis was observed. We diagnosed the patient as having a resectable cancer, and performed distal gastrectomy with D2 lymphadenectomy.